Is there Enough room for Non-Invasive Ventilation in Pulmonary Rehabilitation?

Review Article | DOI: https://doi.org/10.31579/2766-2314/007

Is there Enough room for Non-Invasive Ventilation in Pulmonary Rehabilitation?

  • Laura D Ciobanu 1*

Associate Professor, Department of Internal Medicine, University of Medicine and Pharmacy, 700115 Iasi, Romania.

*Corresponding Author: Laura D Ciobanu, Associate Professor, Department of Internal Medicine, University of Medicine and Pharmacy, Grigore T Popa, Iasi; 700115 Iasi, Romania.

Citation: Laura D Ciobanu, (2020) Is there enough room for non-invasive ventilation in pulmonary rehabilitation? J, Biotechechnology and Bioprocessing 1(2); DOI: 10.31579/2766-2314/007

Copyright: © 2020, Laura D Ciobanu, This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Received: 26 October 2020 | Accepted: 28 November 2020 | Published: 02 December 2020

Keywords: chronic obstructive pulmonary disease; pulmonary rehabilitation; non-invasive ventilation

Abstract

Pulmonary rehabilitation (PR) is a non-pharmacological intervention addressed to chronic obstructive pulmonary disease (COPD) and non-COPD chronic respiratory patients, a key management strategy scientifically demonstrated to improve exercise capacity, dyspnoea, health status and psychological wellbeing. The main body of literature comes from COPD patients, as they provide the core evidence for PR programmes. PR is recommended even to severe patients having chronic respiratory failure; their significant psychological impairment and potential for greater instability during the PR programme will be carefully considered by the multidisciplinary team. Optimizing medical management (e g, inhaled bronchodilators, oxygen therapy, non- invasive ventilation) may enhance the results of exercise training. Patients who already receive long-term domiciliary non- invasive ventilation (NIV) for chronic respiratory failure might exercise with NIV during exercise training if acceptable and tolerable to the patient. It is not advisable to offer long-term domiciliary NIV with the only aim to improve outcomes during PR course. There are different attempts to use both negative and positive NIV in limited clinical studies. Long-term adherence to exercise is an important goal of PR programmes and teams, targeting to translate all-domain gains of PR into increased physical activity and participation to real life. Being a reliable alternative for the future, studies should focus on pressure regimens, type of devices, acceptability and portability for everyday activities.

Abbreviations

AECOPD – acute exacerbation of chronic obstructive pulmonary disease

BiPAP – bilevel positive airway pressure 
COPD – chronic obstructive pulmonary disease
CPAP – continuous positive airway pressure
CHRF – chronic hypercapnic respiratory failure
EPAP - expiratory positive airway pressure
FEV1 – forced expiratory volume in 1 second
GOLD – The Global Initiative for Chronic Obstructive Lung Disease
HOT-HMV – home oxygen therapy and home mechanical ventilation
HMV – home mechanical ventilation
HRQoL – health-related quality of life
ICU – intensive care unit
LTOT – long-term oxygen therapy
MIE – mechanical insufflation-exsufflation
6MWT – six-minute walking test
NIV – non-invasive ventilation
NPPV – non-invasive positive pressure ventilation
NPV – negative pressure ventilation
PaCO2 – arterial partial pressure of carbon dioxide
PAP – positive airway pressure
PAV – proportional assist ventilation
pNIV – portable non-invasive ventilation
PR – pulmonary rehabilitation
SpO2% - saturation of arterial blood with oxygen measured by pulse oximetry

The concept of pulmonary rehabilitation briefly

Pulmonary rehabilitation is described as a “comprehensive intervention based on a thorough patient assessment followed by patient-tailored therapies that include, but are not limited to, exercise training, education, and behaviour change, designed to improve the physical and psychological condition of people with chronic respiratory disease, and to promote the long-term adherence to health-enhancing behaviours” [1]. The main goal for PR programmes is to enhance physical activity towards normal levels, to return the patient to the highest possible capacity in order to achieve the maximum level of independence and functioning in the community [2, 3]. Despite being a cost-beneficial intervention, only approximately two-fifth of chronic respiratory patients have been informed by their health care provider about PR and its positive results. This might be an explanation why < 2>

COPD is a leading cause of morbidity and mortality, with an increased burden of disease worldwide and constitutes a major healthcare concern [5, 6]. COPD patients are referred to PR due to persistent respiratory symptoms and/or limited activities of daily living and an unsatisfactory response to medical treatment offered in primary care [7]. PR addresses breathlessness, the perceived discomfort of breathing, a common symptom to many respiratory and systemic diseases [8]. Breathlessness is the consequence of imbalance between the increased respiratory muscle load and reduced ventilatory capacity [8]. Neural respiratory drive, the electrical output from the brainstem to the respiratory muscles, increases in response to this imbalance and acts to maintain an appropriate ventilation, thus becoming a major contributor to the subjective breathlessness [8, 9]. Breathlessness occurs in COPD, with disease advancement or in AECOPD as a result of imbalance in the load-capacity- drive relationship of the ventilatory system [8], with dynamic hyperinflation and impaired gas exchange that worsen ventilation- perfusion mismatch [10]. 

COPD is known to induce, apart from respiratory symptoms, a decrease in muscle strength and endurance due to systemic inflammation, vulnerability to fatigue and a decline in exercise capacity and cardiac function [9, 11, 12, and 13]. A decrease in physical activity and the consecutive sedentary life, along to the weakened pulmonary function, will result in a vicious cycle with decline in health-related quality of life (HRQoL) and physical ability at a disproportionate rate comparing to the decline of lung function [11]. Therefore, COPD has extensively been reported as a complex disease affecting patients’ health beyond the lungs with multiple intrapulmonary and extra pulmonary components and considerable variability between individuals [2].

Multidisciplinary PR is a key component in the management of COPD [5], and has proved to be beneficial in patients with COPD in terms of improving exercise capacity, symptoms (as breathlessness, fatigue, and mood) and HRQoL [14, 15]; it reduces health care utilization, being one of the most cost-effective therapeutic strategies [5, 12]. PR is addressed to stable patients especially with moderate-to-severe disease, after an acute exacerbation, in intensive care unit, in perioperative period after a lung transplantation, before and after lung cancer surgery, and before endobronchial lung volume reduction [12]. It can be offered in a hospital- based outpatient setting, in an inpatient setting, a community-based setting and at the patient’s home [4].

Large differences in results may arise from exercise type, level of supervision, education and physiotherapy strategies, psychological support, use of medication and mostly of duration and frequency of the maintenance programmes [14]. The longer the duration of the PR programmes the greater sustained benefits in comparison with the shorter ones [14]. A contribution may have the patients’ adherence to the programme, severity of disease, comorbidities, and accessibility of the PR premises [14]. These benefits tend to wane over time and most measures of improvement return to baseline by 12-24 months [5, 14]. Therefore, experts recommend continuation of exercise training beyond initial PR in order to prevent a decline in exercise capacity [14]. Maintenance programmes may consist in simple techniques used in ambulatory, community, or home programmes [14]. Home-based exercise interventions are safe and beneficial, helpful for patients who lack access to or are unable to participate in centre-based PR programmes; the increase on PA derives from factors around the patients, like an active spouse, walking the dog and other pets, and grand parenting [16].

Exercise training is the cornerstone in PR programmes and the best approach for increasing muscle strength, decreasing symptoms, reducing mood abnormalities, improving cardiovascular function and the motivation for physical activity [12]. The target training intensity in the PR exercise setting is critically dependent on baseline exercise testing, which is associated with a learning effect [16]. The main components of exercise training programmes are endurance and resistance training that should be supervised at least twice weekly, more than 60% to 80% of the maximal work rate, delivered as high-intensity and dynamic, interval and continuous training [9, 12, 13, 17]; in parallel with these supervised sessions, there are recommended five unsupervised sessions of 30 min of PA per week, in line with standard healthy living advice [17]. Typical modes of aerobic exercise are walking or cycling [13]. In stable COPD patients, a combination of endurance and resistance training should be performed to maximize improvement in limb muscle function and whole- body exercise capacity [9].

Non-invasive ventilation or why to think about it

In advanced stages of respiratory disease, patients frequently develop chronic hypercapnic respiratory failure (CHRF). NIV is the standard treatment for patients with CHRF due to COPD and restrictive lung diseases, and a major indication for home mechanical ventilation (HMV) in Europe [6]. COPD patients benefit from NIV once they have COPD GOLD stage III or IV and CHRF (PaCO2 > 6.0 kPa) in a stable clinical condition. Recent pulmonary rehabilitation BTS guidelines [17] suggest that NIV during exercise training should be offered to patients who already receive domiciliary NIV. With increased use of high-pressure NIV for home therapy, the use of NIV during PR would become more feasible.

In patients with chronic hypercapnic respiratory failure, long-term non- invasive positive pressure ventilation (NPPV) improves important physiological variables such as blood gases and lung hyperinflation. Results from clinical studies have shown that NPPV improves exercise capacity, exercise-related dyspnoea, pulmonary cachexia, sleep quality and QRQoL. Moreover, NPPV treatment might be associated with fewer hospital admission and lower overall treatment costs [18]. The best results with long-term NPPV have been noticed in studies using more intensive forms of NPPV, with higher inspiratory pressures and high back-up frequencies that have improved or even normalised hypercapnia [6, 18, 19, and 20].

Köhnlein et al have conducted a study in 2014 with the intention to assess survival in chronic hypercapnic COPD patients using NPPV in addition to standard treatment for at least 6 hours at night and anytime during daytime. The results provided evidence that NPPV addition in a group of stable COPD patients reduces hypercapnia, improves overall survival, exercise capacity and HRQoL over 1 year when comparing with guideline-oriented COPD treatment without NPPV [18]. In the study conducted by Raveling et al in 2018, NIV was initiated in COPD patients in a stable condition and after an episode of acute respiratory failure using BiPAP ventilators [6]. Compliance to the ventilator after 3 months was

6.6 ± 2.0 hours per night and 80% of the patients have used NIV for more than 5 hours per night. A higher body mass index and forced expiratory volume in one second, a lower bicarbonate before NIV initiation, younger age and NIV initiated in stable conditions were independently associated with better survival [6].

In high-pressures, NIV may develop a haemodynamic compromise due to reduced venous return from high intra-thoracic pressures. These factors may affect results of NIV in NIV-naïve patients or in those with compromised cardiac performance [19]. Still, as shown by Dreher et al, high intensity NPPV using a controlled mode of ventilation with a mean inspiratory pressure of 29 mBar is well tolerated by COPD patients with hypercapnic respiratory failure. Hence, high-intensity NPPV is superior to low-intensity NPPV using an inspiratory pressure of 15 mBAR in controlling nocturnal hypoventilation in this population of patients [21]. It is also advantageous in improving dyspnoea during physical activity, lung function and HRQoL [21]. They have been reported two disadvantages of high-intensity NPPV: patients need more days in hospital to acclimatise and there is an increased expiratory leakage comparing to low-intensity NPPV [21].

Types of non-invasive ventilators

Negative airway pressure devices

Techniques to deliver ventilatory support have developed in 19th century and became popular during the polio epidemic in early 20th century [8]. There are two types of negative pressure ventilation (NPV). One is tank ventilation that provides intermittent sub-atmospheric pressure around the whole body. The other one is cuirass ventilator that provides negative pressure only around the chest and creates a gradient pressure between thorax and lower body, which may increase intrathoracic venous return, right cardiac output and lung perfusion [22]. Breathing pattern undergoing cuirass ventilator is a real approximation of the normal physiological breathing, with more natural distribution of air in the lungs. Hence, NPV does not restrict the patients’ activities and they can be more comfortable [22].

Positive airway pressure devices

Positive airway pressure (PAP) devices offer today a consistent solution; they unload respiratory system and increase its capacity, with a consecutive reduction in neural respiratory drive and breathlessness [8]. Limitation of negative pressure devices promoted development of PAP devices to deliver continuous positive airway pressure (CPAP) and bi- level pressure support. CPAP delivers a fixed level of positive airway pressure during the whole respiratory cycle [8].

Bi-level pressure support, known as NIV, delivers a positive pressure during expiration and a higher positive pressure during inspiration to support inspiratory effort. PAP devices deliver respiratory support through oronasal or nasal mask interfaces, and not through endotracheal tube or tracheostomy, thus being considered as non-invasive devices [8]. PAP devices have well established benefits in acute and chronic respiratory failure in a large range of conditions, including COPD, obstructive sleep apnoea, obesity-related respiratory failure, progressive neuromuscular disease (NMD) and cardiogenic pulmonary oedema, through restoring respiratory muscles load-capacity balance, promoting alveolar ventilation and improving gas exchange [8].

Non-invasive ventilation act as an adjunct to pulmonary rehabilitation

NIV may be used as an adjunctive therapy to PR that unloads the respiratory muscles with the aim to increase the intensity of exercise training in selected patients with severe chronic respiratory disease who have a suboptimal response to exercise [1]. The benefits appear to be more marked in patients with severe COPD, and higher tolerated positive pressure may lead to greater improvements [1], with improved exercise performance and reduced breathlessness [23]. COPD is characterized by recurrent exacerbations leading to episodes of severe clinical deterioration requiring hospitalization and ventilatory support. Persistent hypercapnia after an episode of AECOPD is associated with excess mortality and early hospitalization [24]. Non-invasive positive airway pressure (PAP) interventions, applied during exercise, at rest and in the end-of-life setting, can be used to restore the balance of respiratory muscle load and capacity, with reducing neural respiratory drive and dyspnoea [8].

Long-term oxygen therapy (LTOT) and non-invasive ventilation (NIV) are potentially valuable therapeutic options, especially in COPD patients with severe lung hyperinflation and exercise-induced desaturation noticed during exercise training as part of a comprehensive PR programme [16]. For patients with COPD and chronic hypoxia LTOT is crucial in terms of improving survival. In these cases, use of supplemental oxygen during exercise may be associated with reduced exertional SpO2 and increased exercise performance [25]. The addition of nasal positive pressure ventilation to LTOT in hypercapnic patients has been shown to improve arterial blood gases, dyspnoea, quality of life and survival [20, 23]. Oxygen saturation measured by pulse oximetry (SpO2) should be > 88% during exercise; if SpO2 is ≤ 88% while breathing room air, supplemental oxygen should be used to maintain SpO2 at > 88% [13, 26] or > 90

The concept of pulmonary rehabilitation briefly

Pulmonary rehabilitation is described as a “comprehensive intervention based on a thorough patient assessment followed by patient-tailored therapies that include, but are not limited to, exercise training, education, and behaviour change, designed to improve the physical and psychological condition of people with chronic respiratory disease, and to promote the long-term adherence to health-enhancing behaviours” [1]. The main goal for PR programmes is to enhance physical activity towards normal levels, to return the patient to the highest possible capacity in order to achieve the maximum level of independence and functioning in the community [2, 3]. Despite being a cost-beneficial intervention, only approximately two-fifth of chronic respiratory patients have been informed by their health care provider about PR and its positive results. This might be an explanation why < 2>

COPD is a leading cause of morbidity and mortality, with an increased burden of disease worldwide and constitutes a major healthcare concern [5, 6]. COPD patients are referred to PR due to persistent respiratory symptoms and/or limited activities of daily living and an unsatisfactory response to medical treatment offered in primary care [7]. PR addresses breathlessness, the perceived discomfort of breathing, a common symptom too many respiratory and systemic diseases [8]. Breathlessness is the consequence of imbalance between the increased respiratory muscle load and reduced ventilatory capacity [8]. Neural respiratory drive, the electrical output from the brainstem to the respiratory muscles, increases in response to this imbalance and acts to maintain an appropriate ventilation, thus becoming a major contributor to the subjective breathlessness [8, 9]. Breathlessness occurs in COPD, with disease advancement or in AECOPD as a result of imbalance in the load-capacity-drive relationship of the ventilatory system [8], with dynamic hyperinflation and impaired gas exchange that worsen ventilation-perfusion mismatch [10]. 

COPD is known to induce, apart from respiratory symptoms, a decrease in muscle strength and endurance due to systemic inflammation, vulnerability to fatigue and a decline in exercise capacity and cardiac function [9, 11, 12, and 13]. A decrease in physical activity and the consecutive sedentary life, along to the weakened pulmonary function, will result in a vicious cycle with decline in health-related quality of life (HRQoL) and physical ability at a disproportionate rate comparing to the decline of lung function [11]. Therefore, COPD has extensively been reported as a complex disease affecting patients’ health beyond the lungs with multiple intrapulmonary and extra pulmonary components and considerable variability between individuals [2]. 

Multidisciplinary PR is a key component in the management of COPD [5], and has proved to be beneficial in patients with COPD in terms of improving exercise capacity, symptoms (as breathlessness, fatigue, and mood) and HRQoL [14, 15]; it reduces health care utilization, being one of the most cost-effective therapeutic strategies [5, 12]. PR is addressed to stable patients especially with moderate-to-severe disease, after an acute exacerbation, in intensive care unit, in perioperative period after a lung transplantation, before and after lung cancer surgery, and before endobronchial lung volume reduction [12]. It can be offered in a hospital-based outpatient setting, in an inpatient setting, a community-based setting and at the patient’s home [4]. 

Large differences in results may arise from exercise type, level of supervision, education and physiotherapy strategies, psychological support, use of medication and mostly of duration and frequency of the maintenance programmes [14]. The longer the duration of the PR programmes the greater sustained benefits in comparison with the shorter ones [14]. A contribution may have the patients’ adherence to the programme, severity of disease, comorbidities, and accessibility of the PR premises [14]. These benefits tend to wane over time and most measures of improvement return to baseline by 12-24 months [5, 14]. Therefore, experts recommend continuation of exercise training beyond initial PR in order to prevent a decline in exercise capacity [14]. Maintenance programmes may consist in simple techniques used in ambulatory, community, or home programmes [14]. Home-based exercise interventions are safe and beneficial, helpful for patients who lack access to or are unable to participate in centre-based PR programmes; the increase on PA derives from factors around the patients, like an active spouse, walking the dog and other pets, and grand parenting [16].

Exercise training is the cornerstone in PR programmes and the best approach for increasing muscle strength, decreasing symptoms, reducing mood abnormalities, improving cardiovascular function and the motivation for physical activity [12]. The target training intensity in the PR exercise setting is critically dependent on baseline exercise testing, which is associated with a learning effect [16]. The main components of exercise training programmes are endurance and resistance training that should be practised supervised at least twice weekly, more than 60% to 80% of the maximal work rate, delivered as high-intensity and dynamic, interval and continuous training [9, 12, 13, 17]; in parallel with these supervised sessions, there are recommended five unsupervised sessions of 30 min of PA per week, in line with standard healthy living advice [17]. Typical modes of aerobic exercise are walking or cycling [13]. In stable COPD patients, a combination of endurance and resistance training should be performed to maximize improvement in limb muscle function and whole-body exercise capacity [9]. 

Non-invasive ventilation or why to think about it

In advanced stages of respiratory disease, patients frequently develop chronic hypercapnic respiratory failure (CHRF). NIV is the standard treatment for patients with CHRF due to COPD and restrictive lung diseases, and a major indication for home mechanical ventilation (HMV) in Europe [6]. COPD patients benefit from NIV once they have COPD GOLD stage III or IV and CHRF (PaCO2 > 6.0 kPa) in a stable clinical condition. Recent pulmonary rehabilitation BTS guidelines [17] suggest that NIV during exercise training should be offered to patients who already receive domiciliary NIV. With increased use of high-pressure NIV for home therapy, the use of NIV during PR would become more feasible.

In patients with chronic hypercapnic respiratory failure, long-term non-invasive positive pressure ventilation (NPPV) improves important physiological variables such as blood gases and lung hyperinflation. Results from clinical studies have shown that NPPV improves exercise capacity, exercise-related dyspnoea, pulmonary cachexia, sleep quality and QRQoL. Moreover, NPPV treatment might be associated with fewer hospital admission and lower overall treatment costs [18]. The best results with long-term NPPV have been noticed in studies using more intensive forms of NPPV, with higher inspiratory pressures and high back-up frequencies that have improved or even normalised hypercapnia [6, 18, 19, and 20]. 

Köhnlein et al have conducted a study in 2014 with the intention to assess survival in chronic hypercapnic COPD patients using NPPV in addition to standard treatment for at least 6 hours at night and anytime during daytime. The results provided evidence that NPPV addition in a group of stable COPD patients reduces hypercapnia, improves overall survival, exercise capacity and HRQoL over 1 year when comparing with guideline-oriented COPD treatment without NPPV [18]. In the study conducted by Raveling et al in 2018, NIV was initiated in COPD patients in a stable condition and after an episode of acute respiratory failure using BiPAP ventilators [6]. Compliance to the ventilator after 3 months was 6.6 ± 2.0 hours per night and 80% of the patients have used NIV for more than 5 hours per night. A higher body mass index and forced expiratory volume in one second, a lower bicarbonate before NIV initiation, younger age and NIV initiated in stable conditions were independently associated with better survival [6]. 

In high-pressures, NIV may develop a haemodynamic compromise due to reduced venous return from high intra-thoracic pressures. These factors may affect results of NIV in NIV-naïve patients or in those with compromised cardiac performance [19]. Still, as shown by Dreher et al, high intensity NPPV using a controlled mode of ventilation with a mean inspiratory pressure of 29 mBar is well tolerated by COPD patients with hypercapnic respiratory failure. Hence, high-intensity NPPV is superior to low-intensity NPPV using an inspiratory pressure of 15 mBAR in controlling nocturnal hypoventilation in this population of patients [21]. It is also advantageous in improving dyspnoea during physical activity, lung function and HRQoL [21]. They have been reported two disadvantages of high-intensity NPPV: patients need more days in hospital to acclimatise and there is an increased expiratory leakage comparing to low-intensity NPPV [21]. 

Types of non-invasive ventilators

Negative airway pressure devices

Techniques to deliver ventilatory support have developed in 19th century and became popular during the polio epidemic in early 20th century [8]. There are two types of negative pressure ventilation (NPV). One is tank ventilation that provides intermittent sub-atmospheric pressure around the whole body. The other one is cuirass ventilator that provides negative pressure around the chest only and creates a gradient pressure between thorax and lower body, which may increase intrathoracic venous return, right cardiac output and lung perfusion [22]. Breathing pattern undergoing cuirass ventilator is a real approximation of the normal physiological breathing, with more natural distribution of air in the lungs. Hence, NPV does not restrict the patients’ activities and they can be more comfortable [22]. 

Positive airway pressure devices

Positive airway pressure (PAP) devices offer today a consistent solution; they unload respiratory system and increase its capacity, with a consecutive reduction in neural respiratory drive and breathlessness [8]. Limitation of negative pressure devices promoted development of PAP devices to deliver continuous positive airway pressure (CPAP) and bi-level pressure support. CPAP delivers a fixed level of positive airway pressure during the whole respiratory cycle [8]. 

Bi-level pressure support, known as NIV, delivers a positive pressure during expiration and a higher positive pressure during inspiration to support inspiratory effort. PAP devices deliver respiratory support through oronasal or nasal mask interfaces, and not through endotracheal tube or tracheostomy, thus being considered as non-invasive devices [8]. PAP devices have well established benefits in acute and chronic respiratory failure in a large range of conditions, including COPD, obstructive sleep apnoea, obesity-related respiratory failure, progressive neuromuscular disease (NMD) and cardiogenic pulmonary oedema, through restoring respiratory muscles load-capacity balance, promoting alveolar ventilation and improving gas exchange [8]. 

Non-invasive ventilation act as an adjunct to pulmonary rehabilitation

NIV may be used as an adjunctive therapy to PR that unloads the respiratory muscles with the aim to increase the intensity of exercise training in selected patients with severe chronic respiratory disease who have a suboptimal response to exercise [1]. The benefits appear to be more marked in patients with severe COPD, and higher tolerated positive pressure may lead to greater improvements [1], with improved exercise performance and reduced breathlessness [23]. COPD is characterized by recurrent exacerbations leading to episodes of severe clinical deterioration requiring hospitalization and ventilatory support. Persistent hypercapnia after an episode of AECOPD is associated with excess mortality and early hospitalization [24]. Non-invasive positive airway pressure (PAP) interventions, applied during exercise, at rest and in the end-of-life setting, can be used to restore the balance of respiratory muscle load and capacity, with reducing neural respiratory drive and dyspnoea [8]. 

Long-term oxygen therapy (LTOT) and non-invasive ventilation (NIV) are potentially valuable therapeutic options, especially in COPD patients with severe lung hyperinflation and exercise-induced desaturation noticed during exercise training as part of a comprehensive PR programme [16]. For patients with COPD and chronic hypoxia LTOT is crucial in terms of improving survival. In these cases, use of supplemental oxygen during exercise may be associated with reduced exertional SpO2 and increased exercise performance [25]. The addition of nasal positive pressure ventilation to LTOT in hypercapnic patients has been shown to improve arterial blood gases, dyspnoea, quality of life and survival [20, 23]. Oxygen saturation measured by pulse oximetry (SpO2) should be > 88% during exercise; if SpO2 is ≤ 88% while breathing room air, supplemental oxygen should be used to maintain SpO2 at > 88% [13, 26] or > 90

Conclusions

Pulmonary rehabilitation is a unique non-pharmacological therapy addressed to symptomatic COPD and non-COPD patients with a poor HRQoL due to breathlessness and fatigue. Because of dyspnoea, patients become more socially isolated and finally housebound. PR, LTOT and NIV bring hope in this difficult and long-term fight with a chronic respiratory disease, encouraging patients to meet other people with same disability and fear from illness and death, to exercise together and to continue their lives in a better condition. There is enough room, need and available technology to implement NIV worldwide, to encourage both patients and researchers to look ahead and find the best answers for the reported practical problems.

References

Clearly Auctoresonline and particularly Psychology and Mental Health Care Journal is dedicated to improving health care services for individuals and populations. The editorial boards' ability to efficiently recognize and share the global importance of health literacy with a variety of stakeholders. Auctoresonline publishing platform can be used to facilitate of optimal client-based services and should be added to health care professionals' repertoire of evidence-based health care resources.

img

Virginia E. Koenig

Journal of Clinical Cardiology and Cardiovascular Intervention The submission and review process was adequate. However I think that the publication total value should have been enlightened in early fases. Thank you for all.

img

Delcio G Silva Junior

Journal of Women Health Care and Issues By the present mail, I want to say thank to you and tour colleagues for facilitating my published article. Specially thank you for the peer review process, support from the editorial office. I appreciate positively the quality of your journal.

img

Ziemlé Clément Méda

Journal of Clinical Research and Reports I would be very delighted to submit my testimonial regarding the reviewer board and the editorial office. The reviewer board were accurate and helpful regarding any modifications for my manuscript. And the editorial office were very helpful and supportive in contacting and monitoring with any update and offering help. It was my pleasure to contribute with your promising Journal and I am looking forward for more collaboration.

img

Mina Sherif Soliman Georgy

We would like to thank the Journal of Thoracic Disease and Cardiothoracic Surgery because of the services they provided us for our articles. The peer-review process was done in a very excellent time manner, and the opinions of the reviewers helped us to improve our manuscript further. The editorial office had an outstanding correspondence with us and guided us in many ways. During a hard time of the pandemic that is affecting every one of us tremendously, the editorial office helped us make everything easier for publishing scientific work. Hope for a more scientific relationship with your Journal.

img

Layla Shojaie

The peer-review process which consisted high quality queries on the paper. I did answer six reviewers’ questions and comments before the paper was accepted. The support from the editorial office is excellent.

img

Sing-yung Wu

Journal of Neuroscience and Neurological Surgery. I had the experience of publishing a research article recently. The whole process was simple from submission to publication. The reviewers made specific and valuable recommendations and corrections that improved the quality of my publication. I strongly recommend this Journal.

img

Orlando Villarreal

Dr. Katarzyna Byczkowska My testimonial covering: "The peer review process is quick and effective. The support from the editorial office is very professional and friendly. Quality of the Clinical Cardiology and Cardiovascular Interventions is scientific and publishes ground-breaking research on cardiology that is useful for other professionals in the field.

img

Katarzyna Byczkowska

Thank you most sincerely, with regard to the support you have given in relation to the reviewing process and the processing of my article entitled "Large Cell Neuroendocrine Carcinoma of The Prostate Gland: A Review and Update" for publication in your esteemed Journal, Journal of Cancer Research and Cellular Therapeutics". The editorial team has been very supportive.

img

Anthony Kodzo-Grey Venyo

Testimony of Journal of Clinical Otorhinolaryngology: work with your Reviews has been a educational and constructive experience. The editorial office were very helpful and supportive. It was a pleasure to contribute to your Journal.

img

Pedro Marques Gomes

Dr. Bernard Terkimbi Utoo, I am happy to publish my scientific work in Journal of Women Health Care and Issues (JWHCI). The manuscript submission was seamless and peer review process was top notch. I was amazed that 4 reviewers worked on the manuscript which made it a highly technical, standard and excellent quality paper. I appreciate the format and consideration for the APC as well as the speed of publication. It is my pleasure to continue with this scientific relationship with the esteem JWHCI.

img

Bernard Terkimbi Utoo

This is an acknowledgment for peer reviewers, editorial board of Journal of Clinical Research and Reports. They show a lot of consideration for us as publishers for our research article “Evaluation of the different factors associated with side effects of COVID-19 vaccination on medical students, Mutah university, Al-Karak, Jordan”, in a very professional and easy way. This journal is one of outstanding medical journal.

img

Prof Sherif W Mansour

Dear Hao Jiang, to Journal of Nutrition and Food Processing We greatly appreciate the efficient, professional and rapid processing of our paper by your team. If there is anything else we should do, please do not hesitate to let us know. On behalf of my co-authors, we would like to express our great appreciation to editor and reviewers.

img

Hao Jiang

As an author who has recently published in the journal "Brain and Neurological Disorders". I am delighted to provide a testimonial on the peer review process, editorial office support, and the overall quality of the journal. The peer review process at Brain and Neurological Disorders is rigorous and meticulous, ensuring that only high-quality, evidence-based research is published. The reviewers are experts in their fields, and their comments and suggestions were constructive and helped improve the quality of my manuscript. The review process was timely and efficient, with clear communication from the editorial office at each stage. The support from the editorial office was exceptional throughout the entire process. The editorial staff was responsive, professional, and always willing to help. They provided valuable guidance on formatting, structure, and ethical considerations, making the submission process seamless. Moreover, they kept me informed about the status of my manuscript and provided timely updates, which made the process less stressful. The journal Brain and Neurological Disorders is of the highest quality, with a strong focus on publishing cutting-edge research in the field of neurology. The articles published in this journal are well-researched, rigorously peer-reviewed, and written by experts in the field. The journal maintains high standards, ensuring that readers are provided with the most up-to-date and reliable information on brain and neurological disorders. In conclusion, I had a wonderful experience publishing in Brain and Neurological Disorders. The peer review process was thorough, the editorial office provided exceptional support, and the journal's quality is second to none. I would highly recommend this journal to any researcher working in the field of neurology and brain disorders.

img

Dr Shiming Tang

Dear Agrippa Hilda, Journal of Neuroscience and Neurological Surgery, Editorial Coordinator, I trust this message finds you well. I want to extend my appreciation for considering my article for publication in your esteemed journal. I am pleased to provide a testimonial regarding the peer review process and the support received from your editorial office. The peer review process for my paper was carried out in a highly professional and thorough manner. The feedback and comments provided by the authors were constructive and very useful in improving the quality of the manuscript. This rigorous assessment process undoubtedly contributes to the high standards maintained by your journal.

img

Raed Mualem

International Journal of Clinical Case Reports and Reviews. I strongly recommend to consider submitting your work to this high-quality journal. The support and availability of the Editorial staff is outstanding and the review process was both efficient and rigorous.

img

Andreas Filippaios

Thank you very much for publishing my Research Article titled “Comparing Treatment Outcome Of Allergic Rhinitis Patients After Using Fluticasone Nasal Spray And Nasal Douching" in the Journal of Clinical Otorhinolaryngology. As Medical Professionals we are immensely benefited from study of various informative Articles and Papers published in this high quality Journal. I look forward to enriching my knowledge by regular study of the Journal and contribute my future work in the field of ENT through the Journal for use by the medical fraternity. The support from the Editorial office was excellent and very prompt. I also welcome the comments received from the readers of my Research Article.

img

Dr Suramya Dhamija

Dear Erica Kelsey, Editorial Coordinator of Cancer Research and Cellular Therapeutics Our team is very satisfied with the processing of our paper by your journal. That was fast, efficient, rigorous, but without unnecessary complications. We appreciated the very short time between the submission of the paper and its publication on line on your site.

img

Bruno Chauffert

I am very glad to say that the peer review process is very successful and fast and support from the Editorial Office. Therefore, I would like to continue our scientific relationship for a long time. And I especially thank you for your kindly attention towards my article. Have a good day!

img

Baheci Selen

"We recently published an article entitled “Influence of beta-Cyclodextrins upon the Degradation of Carbofuran Derivatives under Alkaline Conditions" in the Journal of “Pesticides and Biofertilizers” to show that the cyclodextrins protect the carbamates increasing their half-life time in the presence of basic conditions This will be very helpful to understand carbofuran behaviour in the analytical, agro-environmental and food areas. We greatly appreciated the interaction with the editor and the editorial team; we were particularly well accompanied during the course of the revision process, since all various steps towards publication were short and without delay".

img

Jesus Simal-Gandara

I would like to express my gratitude towards you process of article review and submission. I found this to be very fair and expedient. Your follow up has been excellent. I have many publications in national and international journal and your process has been one of the best so far. Keep up the great work.

img

Douglas Miyazaki

We are grateful for this opportunity to provide a glowing recommendation to the Journal of Psychiatry and Psychotherapy. We found that the editorial team were very supportive, helpful, kept us abreast of timelines and over all very professional in nature. The peer review process was rigorous, efficient and constructive that really enhanced our article submission. The experience with this journal remains one of our best ever and we look forward to providing future submissions in the near future.

img

Dr Griffith

I am very pleased to serve as EBM of the journal, I hope many years of my experience in stem cells can help the journal from one way or another. As we know, stem cells hold great potential for regenerative medicine, which are mostly used to promote the repair response of diseased, dysfunctional or injured tissue using stem cells or their derivatives. I think Stem Cell Research and Therapeutics International is a great platform to publish and share the understanding towards the biology and translational or clinical application of stem cells.

img

Dr Tong Ming Liu

I would like to give my testimony in the support I have got by the peer review process and to support the editorial office where they were of asset to support young author like me to be encouraged to publish their work in your respected journal and globalize and share knowledge across the globe. I really give my great gratitude to your journal and the peer review including the editorial office.

img

Husain Taha Radhi

I am delighted to publish our manuscript entitled "A Perspective on Cocaine Induced Stroke - Its Mechanisms and Management" in the Journal of Neuroscience and Neurological Surgery. The peer review process, support from the editorial office, and quality of the journal are excellent. The manuscripts published are of high quality and of excellent scientific value. I recommend this journal very much to colleagues.

img

S Munshi

Dr.Tania Muñoz, My experience as researcher and author of a review article in The Journal Clinical Cardiology and Interventions has been very enriching and stimulating. The editorial team is excellent, performs its work with absolute responsibility and delivery. They are proactive, dynamic and receptive to all proposals. Supporting at all times the vast universe of authors who choose them as an option for publication. The team of review specialists, members of the editorial board, are brilliant professionals, with remarkable performance in medical research and scientific methodology. Together they form a frontline team that consolidates the JCCI as a magnificent option for the publication and review of high-level medical articles and broad collective interest. I am honored to be able to share my review article and open to receive all your comments.

img

Tania Munoz

“The peer review process of JPMHC is quick and effective. Authors are benefited by good and professional reviewers with huge experience in the field of psychology and mental health. The support from the editorial office is very professional. People to contact to are friendly and happy to help and assist any query authors might have. Quality of the Journal is scientific and publishes ground-breaking research on mental health that is useful for other professionals in the field”.

img

George Varvatsoulias

Dear editorial department: On behalf of our team, I hereby certify the reliability and superiority of the International Journal of Clinical Case Reports and Reviews in the peer review process, editorial support, and journal quality. Firstly, the peer review process of the International Journal of Clinical Case Reports and Reviews is rigorous, fair, transparent, fast, and of high quality. The editorial department invites experts from relevant fields as anonymous reviewers to review all submitted manuscripts. These experts have rich academic backgrounds and experience, and can accurately evaluate the academic quality, originality, and suitability of manuscripts. The editorial department is committed to ensuring the rigor of the peer review process, while also making every effort to ensure a fast review cycle to meet the needs of authors and the academic community. Secondly, the editorial team of the International Journal of Clinical Case Reports and Reviews is composed of a group of senior scholars and professionals with rich experience and professional knowledge in related fields. The editorial department is committed to assisting authors in improving their manuscripts, ensuring their academic accuracy, clarity, and completeness. Editors actively collaborate with authors, providing useful suggestions and feedback to promote the improvement and development of the manuscript. We believe that the support of the editorial department is one of the key factors in ensuring the quality of the journal. Finally, the International Journal of Clinical Case Reports and Reviews is renowned for its high- quality articles and strict academic standards. The editorial department is committed to publishing innovative and academically valuable research results to promote the development and progress of related fields. The International Journal of Clinical Case Reports and Reviews is reasonably priced and ensures excellent service and quality ratio, allowing authors to obtain high-level academic publishing opportunities in an affordable manner. I hereby solemnly declare that the International Journal of Clinical Case Reports and Reviews has a high level of credibility and superiority in terms of peer review process, editorial support, reasonable fees, and journal quality. Sincerely, Rui Tao.

img

Rui Tao

Clinical Cardiology and Cardiovascular Interventions I testity the covering of the peer review process, support from the editorial office, and quality of the journal.

img

Khurram Arshad